Human acute leukemic cells can be divided on the basis of replication kinetics into proliferative and quiescent subpopulations. The majority of antitumor agents are most effective against proliferating cells, and S-phase active drugs such as cytosine arabinoside are only active against cycling cells. Hence, the presence of a large population of noncycling cells makes chemotherapy more difficult. We have developed methods (using centrifugal elutriation and fluorescence activated cell sorting) to obtain proliferative and quiescent subpopulations of human acute leukemic cells for study. These two subpopulations will be studied with respect to the uptake, activation, and effects on clonogenicity of antileukemic drugs. Additionally, levels of such potential intracellular regulators of proliferation such as cyclic nucleotides, polyamines, thymidine kinase, and energy (nucleotide triphosphate) levels will be compared. The effects of rendering the proliferative cells quiescent and stimulating the quiescent cells to proliferate upon the previously described parameters will be studied. In the final phase of these studies, the proliferative kinetics of leukemic cells growing in vivo within diffusion chambers in mice will be altered and the effects of such manipulations on chemotherapeutic responsiveness will be determined.